Current Status of the Insecticide Resistance in Aedes aegypti (Diptera: Culicidae) from Mexico

The mosquito Aedes aegypti (Diptera: Culicidae) is the primary vector of dengue in Mexico and lately virus Chikungunya, although Aedes albopictus is widely distributed; its role in both diseases’ transmission has not been confirmed. The control of mosquitoes in Mexico includes source reduction consisting in the elimination of containers that are favorable sites for oviposition and development of the aquatic stage. The use of insecticides is to control larvae and adulticides as outdoor ultra-low volume applications and indoor residual spray and more recently impregnated materials. The health department regulates the use of insecticides, and such regulations are revised and adapted over time. Since 1999, the vector control regulations gave preference to the use of pyrethroids, a permethrin-based formulation to control adult forms. This insecticide was used as the only adulticide in Mexico for more than 10 years. The consequences of this actions have evolved in a widespread and strong resistance to other insecticides, mainly pyrethroids. We include in this revision evidence of resistance reported in Ae. aegypti in Mexico

Medical diagnostic methods applied to a medieval female with vitamin D deficiency from the North of Spain

Vitamin D deficiency is a pathological condition that affects bone metabolism by preventing proper mineralization, which eventually leads to bone deformities and other pathological conditions such as osteoporosis, increased bone fragility and fractures. The aim of this study is to present a case of vitamin D deficiency, but also to note how the application of several complementary techniques is a fundamental step in the establishing an accurate diagnosis. These techniques range from classical palaeopathological analysis to modern clinical practice. After the macroscopic examination of a medieval female skeleton from Palencia (Spain), where various bone deformations were observed, a differential diagnosis could not establish a definitive cause. Radiological, bone density, and histological studies were carried out, finally allowing to confirm a vitamin D deficiency suffered in both childhood and adulthood. This is a clear example, with practical applications, of the importance of interdisciplinarity to reveal insights about the life history and physical health of ancient individuals

Research Priorities for Neglected Infectious Diseases in Latin America and the Caribbean Region

Dujardin, J. C. et al. 5 p.-1 tab.Global priorities for research in neglected infectious diseases (NIDs) can be assessed in different ways, but it is important to realize that regional priorities may significantly differ one from another. The region of Latin America and the Caribbean (LAC) is—along with Africa and Asia—more affected by NIDs than other regions of the world. Some of the Latin American NIDs are common to other continents, while others are very specific or disproportionately affect the Latin American region [1– 3] (Table 1). Because of its huge ecological diversity, ongoing environmental changes, and massive migrations, LAC is also a catalyst for the (re-)emergence and spreading of NIDs, both inside and outside the subcontinent. Following a colloquium on NIDs in LAC held in Lima, Peru, between 12 and 14 November 2009, a thematic workshop was organized with the support of the European Commission (EC). It involved 29 scientists (16 from the Americas, two from the Democratic Republic of Congo and India, respectively, and nine from Europe) working on different NIDs and representing several research areas from basic to applied. This report summarizes the consensus comments of the expert group after oral and written consultation. It is envisaged that this document should stimulate a debate within the scientific community and serve as a recommendation for future actions by international or regional funding agencies in the area of NIDs in LACThis work was supported by the Directorate-General for Development Cooperation of the Belgian Government (framework agreement 03, project 95502) and the European CommissionPeer reviewe

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

SuperCam Calibration Targets: Design and Development

SuperCam is a highly integrated remote-sensing instrumental suite for NASA’s Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Vitamin D3 Loaded Niosomes and Transfersomes Produced by Ethanol Injection Method: Identification of the Critical Preparation Step for Size Control

Vesicular nanocarriers have an important role in drug delivery and dietary supplements. Size control and optimization of encapsulation efficiency (EE) should be optimized for those applications. In this work, we report on the identification of the crucial step (injection, evaporation, or sonication) innanovesicles (transfersomes and niosomes) preparation by theethanol injection method (EI). The identification of each production step on the final vesicle size was analyzed in order to optimize further scale-up process. Results indicated that the final size of transfersomeswas clearly influenced by the sonication step while the final size of niosomes was mainly governed by the injection step. Measurements of final surface tension of the different vesicular systems prepared indicate a linear positive tendency with the vesicle size formed. This relation could help to better understand the process and design a vesicular size prediction model for EI. Vitamin D3 (VitD3) was encapsulated in the systems formulated with encapsulation efficiencies larger than 90%. Interaction between the encapsulated compound and the membrane layer components is crucial for vesicle stability. This work has an impact on the scaling-up production of vesicles for further food science applications

Easy-to-perform and cost-effective fabrication of continuous-flow reactors and their application for nanomaterials synthesis

The translation of continuous-flow microreactor technology to the industrial environment has been limited by cost and complexity of the fabrication procedures, and the requirement for specialised infrastructure. In the present study, we have developed a significantly cost-effective and easy-to-perform fabrication method for the generation of optically transparent, continuous-flow reactors. The method combines 3D printing of master moulds with sealing of the PDMS channels’ replica using a pressure-sensitive adhesive tape. Morphological characterisation of the 3D printed moulds was performed, and reactors were fabricated with an approximately square-shaped cross-section of 1 mm^2. Notably, they were tested for operation over a wide range of volumetric flow rates, up to 20 ml/min. Moreover, the fabrication time (i.e., from design to the finished product) was <1 day, at an average material cost of ~£5. The flow reactors have been applied to the production of both inorganic nanoparticles (silver nanospheres) and organic vesicular systems (liposomes), and their performance compared with reactors produced using more expensive and laborious fabrication methods. Numerical simulations were performed to characterise the transport of fluids and chemical species within the devices. The developed fabrication method is suitable for scaled-up fabrication of continuous-flow reactors, with potential for application in biotechnology and nanomedicine

Continuous flow production of size-controllable niosomes using a thermostatic microreactor

The new roles of vesicular systems in advanced biomedical, analytical and food science applications demand novel preparation processes designed to reach the new standards. Particle size and monodispersity have become essential properties to control. In this work, key parameters, involved in a microfluidic reactor with hydrodynamic flow focusing, were investigated in order to quantify their effects on niosomes morphology. Particular attention was given to temperature, which is both a requirement to handle non-ionic surfactants with phase transition temperature above RT, and a tailoring variable for size and monodispersity control. With this aim, niosomes with two different sorbitan esters and cholesterol as stabilizer were formulated. High resolution and conventional 3D-printing technologies were employed for the fabrication of microfluidic reactor and thermostatic systems, since this additive technology has been essential for microfluidics development in terms of cost-effective and rapid prototyping. A customised device to control temperature and facilitate visualization of the process was developed, which can be easily coupled with commercial inverted microscopes. The results demonstrated the capability of microfluidic production of niosomes within the full range of non-ionic surfactants and membrane stabilizers